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Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding
The immunosuppressive drug cyclosporin A (CsA) binds to its receptor protein cyclophilin 18 (Cyp18) in two distinct kinetic phases, while the mechanism remains elusive. Stopped-flow measurements coupled with titration and competition experiments were used to investigate the puzzling two-phase proces...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833397/ https://www.ncbi.nlm.nih.gov/pubmed/27082870 http://dx.doi.org/10.1371/journal.pone.0153669 |
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author | Lin, Weilin Quintero, Andres Zhang, Yixin |
author_facet | Lin, Weilin Quintero, Andres Zhang, Yixin |
author_sort | Lin, Weilin |
collection | PubMed |
description | The immunosuppressive drug cyclosporin A (CsA) binds to its receptor protein cyclophilin 18 (Cyp18) in two distinct kinetic phases, while the mechanism remains elusive. Stopped-flow measurements coupled with titration and competition experiments were used to investigate the puzzling two-phase process of CsA and Cyp18 interaction. This study leads to the dissection of different conformational fractions of either direct fast binding or slow binding with rate-limiting conformational inter-conversion and the real-time measurement of k(on) value (8.34 ± 0.22 x10(6) M(-1)s(-1)) in solution. Furthermore, our study indicates that the structure of CsA during dissociation from the protein possesses a distribution of conformations different from those in solution under equilibrium condition. |
format | Online Article Text |
id | pubmed-4833397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48333972016-04-22 Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding Lin, Weilin Quintero, Andres Zhang, Yixin PLoS One Research Article The immunosuppressive drug cyclosporin A (CsA) binds to its receptor protein cyclophilin 18 (Cyp18) in two distinct kinetic phases, while the mechanism remains elusive. Stopped-flow measurements coupled with titration and competition experiments were used to investigate the puzzling two-phase process of CsA and Cyp18 interaction. This study leads to the dissection of different conformational fractions of either direct fast binding or slow binding with rate-limiting conformational inter-conversion and the real-time measurement of k(on) value (8.34 ± 0.22 x10(6) M(-1)s(-1)) in solution. Furthermore, our study indicates that the structure of CsA during dissociation from the protein possesses a distribution of conformations different from those in solution under equilibrium condition. Public Library of Science 2016-04-15 /pmc/articles/PMC4833397/ /pubmed/27082870 http://dx.doi.org/10.1371/journal.pone.0153669 Text en © 2016 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lin, Weilin Quintero, Andres Zhang, Yixin Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title | Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title_full | Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title_fullStr | Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title_full_unstemmed | Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title_short | Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding |
title_sort | conformational heterogeneity of cyclosporin a in cyclophilin 18 binding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833397/ https://www.ncbi.nlm.nih.gov/pubmed/27082870 http://dx.doi.org/10.1371/journal.pone.0153669 |
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